DEVBIO CHAP 3

• These sexual cycles are controlled by the hypothalamus.
• Gonadotropin-releasing hormone (GnRH).

  Produced by the hypothalamus, acts on cells of the anterior lobe (adenohypophysis) of the pituitary gland, which in turn secrete gonadotropins.
• These hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stimulate and control cyclic changes in the ovary.
• At the beginning of each ovarian cycle, 15 to 20 primary-stage (preantral) follicles are stimulated to grow under the influence of FSH. FSH rescues 15 to 20 of these cells from a pool of continuously forming primary follicles.
• Under normal conditions, only one of these follicles reaches full maturity, and only one oocyte is discharged; the others degenerate and become atretic. In the next cycle, another group of primary follicles is recruited, and again, only one follicle reaches maturity. Consequently, most follicles degenerate without ever reaching full maturity.
• When a follicle becomes atretic, the oocyte and surrounding follicular cells degenerate and are replaced by connective tissue, forming a corpus atreticum. FSH also stimulates maturation of follicular (granulosa) cells surrounding the oocyte.
• In cooperation, theca interna and granulosa cells produce estrogens: Theca interna cells produce androstenedione and testosterone, and granulosa cells convert these hormones to estrone and 17 B estradiol
• As a result of this estrogen production:

  The uterine endometrium enters the follicular or proliferative phase.

  Thinning of the cervical mucus occurs to allow passage of sperm.

  The anterior lobe of the pituitary gland is stimulated to secrete LH.
• At midcycle, there is an LH surge that:

  Elevates concentrations of maturation promoting factor, causing oocytes to complete meiosis I and initiate meiosis II

  Stimulates production of progesterone by follicular stromal cells (luteinization)

  Causes follicular rupture and ovulation
• Under the influence of FSH and LH, the vesicular follicle undergoes rapid growth, reaching a diameter of 25 mm, becoming a mature vesicular (graafian) follicle.
• A surge in LH triggers the completion of meiosis I in the primary oocyte and propels the follicle into the preovulatory mature vesicular stage. Meiosis II is initiated, but the oocyte is arrested in metaphase, about 3 hours before ovulation. The ovary's surface bulges, forming the stigma, an avascular spot at the apex.
• The increased LH concentration induces collagenase activity, leading to the digestion of collagen fibers around the follicle. Additionally, elevated prostaglandin levels, in response to the LH surge, cause local muscular contractions in the ovarian wall.
• Those contractions extrude the oocyte, which together with its surrounding granulosa cells from the region of the cumulus oophorus breaks free (ovulation) and floats out of the ovary. Some of the cumulus oophorus cells then rearrange themselves around the zona pellucida to form the corona radiata.
• CORPUS LUTEUM: After ovulation, remaining granulosa cells and theca interna cells in the ruptured follicle become vascularized by surrounding vessels. Influenced by LH, these cells transform into lutein cells, forming the corpus luteum.
• The corpus luteum secretes estrogen and progesterone.
• Progesterone, along with some estrogen, induces the uterine mucosa to enter the progestational or secretory stage, preparing for embryo implantation.
• OOCYTE TRANSPORT: During the pre-ovulation period, the fimbriae of the uterine tube sweep over the ovary's surface, and the tube contracts rhythmically. The oocyte, accompanied by granulosa cells, is believed to be transported into the tube through the sweeping movements of the fimbriae and ciliary motion on the epithelial lining. * The transport rate is influenced by the endocrine status during and after ovulation.
• In humans, the fertilized oocyte reaches the uterine lumen approximately 3 to 4 days after ovulation.
• CORPUS ALBICANS : If fertilization does not occur, the corpus luteum reaches maximum development approximately 9 days after ovulation. It can easily be recognized as a yellowish projection on the surface of the ovary. The corpus luteum shrinks because of the degeneration of lutein cells (luteolysis) and forms a mass of fibrotic scar tissue, the corpus albicans.
• If the oocyte is fertilized, degeneration of the corpus luteum is prevented by human chorionic gonadotropin, a hormone secreted by the syncytiotrophoblast of the developing embryo.
• The corpus luteum continues to grow and forms the corpus luteum of pregnancy (corpus luteum graviditatis).
• FERTILIZATION: The process by which male and female gametes fuse, occurs in the ampullary region of the uterine tube.
• Only 1% of sperm deposited in the vagina enter the cervix, where they may survive for many hours.
• Movement of sperm from the cervix to the uterine tube occurs by muscular contractions of the uterus and uterine tube and very little by their own propulsion. The trip from cervix to oviduct can occur as rapidly as 30 minutes or as slow as 6 days
• FERTILIZATION: At ovulation, sperm again become motile, perhaps because of chemoattractants produced by cumulus cells surrounding the egg, and swim to the ampulla where fertilization usually occurs.
• Spermatozoa are not able to fertilize the oocyte immediately upon arrival in the female genital tract but must undergo

  1. Capacitation and
  2. The acrosome reaction to acquire this capability.
• Capacitation is a period of conditioning in the female reproductive tract that in the human lasts approximately 7 hours.
• Capacitation occurs in the uterine tube and involves epithelial interactions between the sperm and the mucosal surface of the tube. During this time, a glycoprotein coat and seminal plasma proteins are removed from the plasma membrane that overlies the acrosomal region of the spermatozoa.
• Only capacitated sperm can pass through the corona cells and undergo the acrosome reaction.
• ACROSOME REACTION: Occurs after binding to the zona pellucida, is induced by zona proteins. This reaction culminates in the release of enzymes needed to penetrate the zona pellucida, including acrosin- and trypsin-like substances.
• The phases of fertilization include the following:

  Phase 1, penetration of the corona radiata

  Phase 2, penetration of the zona pellucida

  Phase 3, fusion of the oocyte and sperm cell membranes
• Phase 1: Penetration of the Corona Radiata Of the 200 to 300 million spermatozoa normally deposited in the female genital tract, only 300 to 500 reach the site offertilization. Only one ofthese fertilizes the egg. It is thought that the others aid the fertilizing sperm in penetrating the barriers protecting the female gamete. Capacitated sperm pass freely through corona cell
• Phase 2: Penetration of the Zona Pellucida

  The zona is a glycoprotein shell surrounding the egg that facilitates and maintains sperm binding and induces the acrosome reaction. Both binding and the acrosome reaction are mediated by the ligand ZP3, a zona protein. Permeability of the zona pellucida changes when the head of the sperm comes in contact with the oocyte surface. This contact results in release of lysosomal enzymes from cortical granules lining the plasma membrane of the oocyte.
• In turn, these enzymes alter properties of the zona pellucida (zona reaction) to prevent sperm penetration and inactivate species-specific receptor sites for spermatozoa on the zona surface. Other spermatozoa have been found embedded in the zona pellucida, but only one seems to be able to penetrate the oocyte.
• Phase 3: Fusion of the Oocyte and Sperm Cell Membranes

  The initial adhesion of sperm to the oocyte is mediated in part by the interaction of integrins on the oocyte and their ligands, disintegrins, on sperm. After adhesion, the plasma membranes of the sperm and egg fuse.
• 1. Cortical and zona reactions. As a result of the release of cortical oocyte granules, which contain lysosomal enzymes, (1) the oocyte membrane becomes impenetrable to other spermatozoa, and (2) the zona pellucida alters its structure and composition to prevent sperm binding and penetration. These reactions prevent polyspermy
• Resumption of the second meiotic division.The oocyte finishes its second meiotic division immediately after entry of the spermatozoon. One of the daughter cells, which receives hardly any cytoplasm, is known as the second polar body; the other daughter cell is the definitive oocyte. Its chromosomes (22 plus X) arrange themselves in a vesicular nucleus known as the female pronucleus.
• Metabolic activation of the egg. The activating factor is probably carried by the spermatozoon. Activation encompasses the initial cellular and molecular events associated with early embryogenesis.
• During growth of male and female pronuclei (both haploid), each pronucleus must replicate its DNA. If it does not, each cell of the two-cell zygote has only half of the normal amount of DNA. Immediately after DNA synthesis, chromosomes organize on the spindle in preparation for a normal mitotic division.
• Restoration of the diploid number of chromosomes, half from the father and half from the mother. Hence, the zygote contains a new combination of chromosomes different from both parents